Large organic ring structures are known materials useful as chelating agents for selective binding and extraction of cations and as antioxidants. A number of other uses are recited in the recent review article by K. E. Krakowiak, et al., "Synthesis of Aza-Crown Ethers," Chemical Reviews, Vol. 89, No. 4, 1989, pp. 929-972, including use as key intermediates in the synthesis of cryptands and other N-substituted ligands.
Unfortunately, previous routes to producing the diaza crown ethers are very tedious and expensive, as outlined in the K. E. Krakowiak, et al. article. This publication notes that diaza crown ethers can be prepared by several different routes, for example, reacting 1,2-bis(2-haloethoxy)ethane or triethylene glycol ditosylates with triethylene glycol diamine or bis-(tosylamides) followed by removal of the pendant tosyl groups, if required. Another route concerns reacting a secondary amine with a 1,2-bis(2-haloethoxy)ethane followed by removal of the pendant alkyl groups; or reacting triethylene glycol diamine with triglycolyl dichloride. A number of other methods are described.
C. J. Pedersen, "Cyclic Polyethers and Their Complexes with Metal Salts," Journal of American Chemical Society, Vol. 89, No. 26, Dec. 20, 1967, pp. 7017-7036, describes the synthesis of 33 cyclic polyethers, derived from aromatic vicinal diols and containing 9 to 60 atoms including 3 to 20 oxygen atoms in the ring. Some of the compounds were prepared in good yields without the use of a high-dilution technique. Fifteen of the compounds have been catalytically hydrogenated to the corresponding saturated cyclic polyethers. Many of those containing 5 to 10 oxygen atoms form stable complexes with some or all of the cations of: Li, Na, NH.sub.4, RNH.sub.3, K, Rb, Cs, Ag(I), Au(I), Ca, Sr, Ba, Cd, Hg(I), Hg(II), La(III), Tl(I), Ce(III) and Pb(II). Many of these complexes could be isolated in the crystalline form depending on the anion. They appeared to be salt-polyether complexes formed by ion-dipole interaction between the cation and the negatively charged oxygen atoms of the polyether ring. The stoichiometry of the complexes is one molecule of polyether per single ion regardless of the valence. Some of the polyethers, by complexing, solubilize inorganic compounds, such as potassium hydroxide and permanganate, in aromatic hydrocarbons.
The preparation of cyclic dioxamides has been studied in O. Vogl, et al., "Polyoxamides. I. Polymerization of Cyclic Diamides," Macromolecules, Vol. 1, No. 4, July-August, 1968, pp. 311-315. After reviewing all the methods available to them, they chose the high dilution method using oxalyl chloride and diamine. Even though the high dilution technique was used, their yields of cyclic oxamide were very low. Attempts to prepare the cyclics from ethyl (or methyl) oxalate and hexamethylenediamine hydrochloride directly failed. Also of interest is O. Vogl, et al., "Polyoxamides. II. Polymerization of Cyclic Diamides," Macromolecules, Vol. 1, No. 4, July-August, 1968, pp. 315-318.
Certain oxamides are set out in R. M. Izatt, et al., "Thermodynamic and Kinetic Data for Macrocycle Interaction with Cations and Anions," Chem. Rev., 1991, pp. 1721-1777, but the unique oxamides of the present invention are not set forth.
As may be seen by reviewing the above-noted preparations, macrocyclic oxamides prepared by conventional methods often require more than one step, high dilution conditions and more than one reagent. All of these considerations increase the cost of the produced cyclic oxamides. Note that the Pedersen article discusses the desirability of avoiding high dilution techniques; Vogl, et al. were unable to avoid it. It would be desirable if cyclic oxamides could be prepared by a one-step procedure which did not require high dilution.